The effects of cocaine and other psychomotor stimulants on a number of physiological parameters are being studied in conscious squirrel monkeys and rats. Recent studies in squirrel monkeys have indicated that alpha-1 adrenergic mechanisms are importantly involved in the pressor effects of both cocaine and methamphetamine, while both beta-1 and beta-2 adrenergic mechanisms are important for the tachycardiac effect of both drugs. Based on these studies, the alpha-1 antagonist prazocin would appear to be an ideal drug for the treatment of cardiovascular complications due to psychomotor stimulant abuse. Unlike with cocaine, dopaminergic mechanisms have been shown to be importantly involved in the cardiovascular effects of methamphetamine. In addition, recent studies have also indicated that, contrary to our previous findings, central mechanisms do appear to be significantly involved in the cardiovascular effects of cocaine in squirrel monkeys. The studies using conscious rats indicate that cocaine increases blood pressure and heart rate similar to its effects in squirrel monkeys. Further, a single injection of cocaine produces rapid sensitization to the pressor effects of its subsequent injections administered at 24 hr intervals. The cardiovascular effects of cocaine in rats are completely antagonized by noncompetitive or mixed type autonomic ganglionic blockers, while these effects are partially antagonized by the competitive ganglionic blockers. Cocaine also potentiates the peripheral cardiovascular effects of norepinephrine and inhibits the effects of tyramine, however, these effects occur at doses that are 10 times larger than those doses of cocaine alone required to produce cardiovascular effects. Thus, these results provide substantial evidence that the cardiovascular effects of cocaine in conscious rats are mainly centrally medicated. Acute lethality studies indicate that various adrenergic agents modify acute cocaine intoxication. As with the cardiovascular effects in squirrel monkeys, prazocin was particularly effective against cocaine lethality.